Clostridium difficile infection is a major healthcare burden. It is a major cause of morbidity in the hospitalized elderly and is almost exclusively associated with antimicrobial therapy. C. difficile infection (CDI) may range in severity from mild antibiotic-associated diarrhea/colitis to life-threatening pseudomembranous colitis (Borriello, S. P. 1998. J Antimicrob Chemother. 41 (Suppl. C), 13-19). Treatment strategies for CDI have changed little over the past two decades: oral metronidazole (250-500 mg TID or QID) or vancomycin (125 mg QID) are most commonly used to treat CDI (Wilcox, M. H. 1998. J Antimicrob Chemother. 41 (Suppl. C), 41-46; see also the website postgradmed.com/issues/2002/11—02/joyce3.htm).
C. difficile sporulates to form bacterial spores that are resistant to extremes of heat, radiation, chemical assault, desiccation and time (Aronson, A. I, Fitz-James, P. 1976. Bacteriol Rev. 40, 360-402). C. difficile spores are known to survive in the nosocomial environment and are thought to play a role in transmission of the organism. Moreover, C. difficile spores are recalcitrant to antimicrobial therapy (including metronidazole (MET) and vancomycin (VAN) treatment) and may play a role in recurrent CDI following the cessation of the antibiotic used to treat an initial episode (Walters, B. A. 1983. Gut. 24, 206-212). However, few studies have evaluated antimicrobial activity against C. difficile spores, and the need for therapies that may be used to kill or block germination of C. difficile spores is great.